Raiyyan Tahsan

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TC(813).(06).Psychiatry Case No 24. Anorexia Nervosa

Anorexia Nervosa কী?

Anorexia Nervosa (AN) হলো একটি eating disorder যেখানে রোগী ইচ্ছাকৃতভাবে খাবার কমায়/এড়িয়ে চলে, ফলে significantly low body weight হয়; কিন্তু ওজন বাড়ার ভয় ও body image distortion থাকে। DSM-5-TR অনুযায়ী মূল ৩টি বিষয়: খাবার/ক্যালরি restriction → low body weight, ওজন বাড়ার তীব্র ভয়, এবং নিজের body weight/shape সম্পর্কে distorted perception বা অসুস্থতার গুরুত্ব অস্বীকার।

১) Cause / Etiology ও Pathophysiology

Anorexia Nervosa একক কারণে হয় না; সাধারণত genetic + neurobiological + psychological + socio-cultural factor একসাথে কাজ করে।

প্রধান কারণ/ঝুঁকি:

  1. Genetic predisposition: পরিবারে eating disorder, anxiety, OCD, depression থাকলে ঝুঁকি বাড়ে।
  2. Psychological factor: perfectionism, low self-esteem, excessive self-control, anxiety/OCD traits.
  3. Sociocultural factor: thin body ideal, social media pressure, modelling/dance/sports যেখানে weight-focused culture থাকে। NICE young people, professional sport, fashion, dance, modelling-কে risk context হিসেবে উল্লেখ করেছে।
  4. Dieting/starvation cycle: শুরুতে diet/weight loss → starvation → obsessive food thoughts, irritability, depression, body image distortion আরও বাড়ে।
  5. Comorbidity: depression, anxiety, OCD, self-harm, substance misuse থাকতে পারে; এগুলো assessment-এ অবশ্যই দেখতে হয়।

২) Symptoms ও Clinical Signs

Symptoms — রোগী যা বলে/করতে দেখা যায়

  • খুব কম খাওয়া, খাবার avoid করা, calorie counting
  • ওজন বাড়ার তীব্র ভয়, বারবার weight check
  • নিজেকে মোটা মনে করা, যদিও underweight
  • খাবার নিয়ে ritual: ছোট টুকরা করা, ধীরে খাওয়া, লুকিয়ে ফেলা
  • excessive exercise
  • vomiting, laxative/diuretic misuse — binge-purge subtype হলে
  • amenorrhea/irregular menstruation, libido কমে যাওয়া
  • ঠান্ডা বেশি লাগা, দুর্বলতা, মাথা ঘোরা, syncope
  • constipation, abdominal bloating
  • irritability, depression, anxiety, social withdrawal
  • severe case: suicidal ideation/self-harm risk

Clinical signs — examination-এ যা পাওয়া যায়

  • Low BMI বা expected weight-এর তুলনায় কম weight
  • Bradycardia, hypotension, postural hypotension
  • Hypothermia
  • Dry skin, hair loss, lanugo hair
  • Peripheral cyanosis/acrocyanosis, cold extremities
  • Muscle wasting, weakness
  • Dehydration
  • Parotid enlargement, dental erosion, Russell’s sign — vomiting থাকলে
  • Peripheral edema — refeeding বা hypoalbuminaemia-related
  • Delayed puberty/faltering growth — children/adolescents
  • Osteopenia/osteoporosis risk

NICE অনুযায়ী malnutrition-এর physical signs যেমন dizziness, palpitations, fainting, pallor এবং compensatory behaviour যেমন vomiting/laxative/diuretic misuse, excessive exercise clinical suspicion বাড়ায়।

৩) Clinically Diagnosis — কীভাবে diagnosis করবেন

DSM-5-TR Diagnostic Criteria

A. Energy intake restriction → age/sex/development অনুযায়ী significantly low body weight
B. Weight gain বা “fat” হওয়ার intense fear, অথবা weight gain বাধা দেয় এমন persistent behaviour
C. Body weight/shape perception disturbance, self-evaluation-এ weight/shape-এর excessive influence, অথবা low weight-এর seriousness অস্বীকার

Subtype

  • Restricting type: dieting/fasting/excessive exercise; regular binge/purge নেই
  • Binge-eating/purging type: binge eating বা vomiting/laxative/diuretic misuse থাকে

Severity — adult BMI দিয়ে ধারণা

  • Mild: BMI ≥17 kg/m²
  • Moderate: BMI 16–16.99
  • Severe: BMI 15–15.99
  • Extreme: BMI <15

তবে admission/management decision শুধু BMI দিয়ে করা যাবে না; vitals, electrolyte, ECG, weight-loss rate, suicidality, organ compromise একসাথে দেখতে হবে। NICE absolute BMI threshold না ব্যবহার করার কথা বলেছে।

৪) Investigation — specific workup

Anorexia Nervosa diagnosis মূলত clinical, কিন্তু investigation লাগে medical complications, differential diagnosis, refeeding risk এবং drug safety দেখার জন্য।

Baseline assessment

  • Height, weight, BMI, % expected body weight
  • Weight-loss rate: কত kg/week বা কত %/3–6 months
  • Pulse, BP lying/standing, temperature
  • Hydration status
  • Menstrual/puberty history
  • Eating pattern, purging, laxative/diuretic, exercise history
  • Depression, anxiety, OCD, self-harm/suicide assessment
  • Substance misuse assessment

Lab tests

  1. CBC: anemia, leukopenia, thrombocytopenia
  2. Serum electrolytes: Na⁺, K⁺, Cl⁻, HCO₃⁻ — vomiting/laxative/diuretic effect
  3. Renal function: urea, creatinine
  4. Glucose: hypoglycaemia
  5. Calcium, magnesium, phosphate: refeeding syndrome risk
  6. LFT: starvation-related transaminitis
  7. Albumin/total protein: nutritional status; normal থাকলেও AN exclude হয় না
  8. TSH, free T4: hyperthyroidism/low T3 syndrome differentiation
  9. ESR/CRP: chronic infection/inflammatory disease suspicion হলে
  10. β-hCG/pregnancy test: reproductive-age female
  11. Vitamin D, B12, folate, ferritin: deficiency assessment
  12. Urinalysis: dehydration, ketones, renal issue
  13. Amylase: vomiting/purging suspicion হলে

NICE eating disorder-এ compensatory behaviour থাকলে fluid/electrolyte balance assess করতে বলেছে এবং significant weight change/purging থাকলে ECG consideration উল্লেখ করেছে।

Cardiac ও bone assessment

  • ECG: bradycardia, QT prolongation, arrhythmia, hypokalaemia risk
  • DEXA scan: children/adolescents-এ ১ বছর underweight থাকলে, adults-এ ২ বছর underweight থাকলে, অথবা bone pain/recurrent fracture থাকলে আগে করা যায়।

Red flag — urgent referral/admission

  • Severe malnutrition, severe dehydration
  • Severe electrolyte imbalance: hypokalaemia, hypophosphataemia, hypomagnesaemia
  • Bradycardia <40/min, prolonged QT, arrhythmia
  • Syncope, hypotension, hypothermia
  • Rapid weight loss, e.g., >1 kg/week
  • Organ failure sign
  • Suicidal risk/self-harm
  • Refeeding syndrome risk

NICE severe electrolyte imbalance, severe malnutrition, severe dehydration বা incipient organ failure থাকলে acute medical care/emergency admission recommend করে।

৫) Differential Diagnosis

Medical causes of weight loss:

  • Hyperthyroidism
  • Type 1 diabetes mellitus
  • Malignancy
  • TB/HIV/chronic infection
  • IBD, coeliac disease, malabsorption
  • Addison disease
  • Chronic liver/kidney disease
  • CNS tumour/chronic neurological disease

Psychiatric differential:

  • Major depressive disorder with appetite loss
  • OCD
  • Body dysmorphic disorder
  • ARFID — body image disturbance নেই
  • Bulimia nervosa — usually weight normal/overweight হতে পারে
  • Psychotic disorder with food-related delusion
  • Substance use disorder

৬) Treatment & Management

Core principle

Anorexia Nervosa-তে ওষুধ একা মূল চিকিৎসা নয়। NICE স্পষ্টভাবে বলেছে: “Do not offer medication as the sole treatment for anorexia nervosa.” মূল চিকিৎসা হলো nutritional rehabilitation + psychotherapy + medical monitoring + family involvement।

Non-pharmacological management

A. Nutritional rehabilitation

  • Goal: medically safe weight restoration
  • Dietitian-supervised meal plan
  • Sudden high-calorie feeding নয়, refeeding risk অনুযায়ী ধীরে calories বাড়ানো
  • Daily/regular monitoring: weight, pulse, BP, temperature, hydration, electrolytes
  • Refeeding syndrome risk হলে phosphate, potassium, magnesium closely monitor

NICE অনুযায়ী healthy body weight/BMI-তে পৌঁছানো key goal, কারণ weight gain psychological, physical ও quality-of-life recovery-তে central role রাখে।

B. Psychotherapy

Adults:

  • CBT-ED: সাধারণত 40 sessions over 40 weeks
  • MANTRA: সাধারণত 20 sessions
  • SSCM: 20 বা বেশি weekly sessions
    NICE adults-    এ CBT-ED, MANTRA বা SSCM consider করতে বলেছে।

Children/adolescents:

  • Family Therapy for Anorexia Nervosa — FT-AN: সাধারণত 18–20 sessions over 1 year
  • Family-based treatment is first-line approach
    NICE children/young people-    এ FT-AN recommend করে।

৭) Pharmacological Management — point আকারে

Important: নিচের medication regimen specialist psychiatrist/medicine physician supervision ছাড়া শুরু করা উচিত নয়, কারণ AN-এ bradycardia, electrolyte imbalance, QT prolongation ও refeeding risk থাকে।

১. Thiamine / Vitamin B1

  • Generic name: Thiamine
  • Tablet 1.Vita-One 100mg AS A Thiamine Hydrochloride AS A Vitamin-B preparations.
  • Dose: 200–300 mg/day PO, usually divided dose
  • Duration: refeeding শুরু করার আগে/সাথে এবং প্রথম 10 দিন; severe malnutrition বা neurological sign থাকলে hospital protocol অনুযায়ী IV high-dose
  • Drug description: Water-soluble vitamin; carbohydrate metabolism-এর cofactor
  • কেন use হয়: Refeeding-এর সময় carbohydrate intake বাড়লে thiamine demand বাড়ে; deficiency হলে Wernicke encephalopathy ও lactic acidosis risk থাকে
  • Side effects: Oral thiamine সাধারণত safe; nausea/GI upset rare; IV দিলে rare anaphylaxis
  • Interaction: clinically major common interaction কম; loop diuretic long-term use thiamine deficiency বাড়াতে পারে
  • Monitoring: Mg, phosphate, K⁺, glucose, fluid balance
  • Clinical note: এটি AN cure করে না; refeeding complication prevention-এর জন্য use হয়। Refeeding syndrome prevention-এ thiamine/B vitamins feeding-এর আগে ও প্রথম 10 দিন দেওয়ার recommendation আছে।

২. Multivitamin + multimineral supplement

  • Generic: Balanced multivitamin/multimineral preparation
  • Tablet 2.Bextrum Gold AS A Multivitamin and Multiminarels AS A Multi-vitamin & Multi-mineral combined preparations.
  • Dose: 1 tablet/capsule PO daily
  • Duration: diet adequate না হওয়া পর্যন্ত; at least early refeeding phase
  • কেন use হয়: Starvation-related micronutrient deficiency correction/prevention
  • Side effects: nausea, constipation/diarrhoea, metallic taste
  • Interaction: iron/calcium/zinc containing preparation levothyroxine, tetracycline, quinolone antibiotic-এর absorption কমাতে পারে; 2–4 hours gap রাখা উচিত
  • Clinical note: NICE AN-এ age-appropriate oral multivitamin and multimineral supplement recommend করে যতদিন diet dietary reference values meet না করে।

৩. Potassium chloride

  • Generic name: Potassium chloride
  • Tablet 3.Electro-K 600mg AS A Electrolytes preparations, Oral electrolytes preparations.
  • Dose: Lab-based. Mild hypokalaemia হলে commonly 20–40 mmol PO; severe/symptomatic hypokalaemia হলে hospital IV replacement with ECG monitoring
  • Duration: serum K⁺ normal হওয়া পর্যন্ত; refeeding phase-এ daily monitoring দরকার
  • কেন use হয়: vomiting/laxative/diuretic misuse বা refeeding syndrome-এ hypokalaemia correct করতে
  • Side effects: nausea, abdominal pain, diarrhoea; IV দিলে phlebitis; overdose → hyperkalaemia, arrhythmia
  • Interaction: ACE inhibitor/ARB, spironolactone/eplerenone, trimethoprim, NSAIDs → hyperkalaemia risk
  • Clinical note: ECG abnormality বা severe hypokalaemia থাকলে outpatient correction unsafe.

৪. Phosphate replacement

  • Generic: Sodium phosphate / potassium phosphate
  • Oral solution 4. Phosphoprep AS A Sodium dihydrogen phosphate + Disodium hydrogen phosphate AS A (2.711 g + 1.2 g / 5 ml) 45 Ml Bottle Enema & bowel cleansing solution.
  • Dose: Serum phosphate ও renal function অনুযায়ী oral/IV protocol; severe hypophosphataemia হলে hospital IV replacement
  • Duration: phosphate normal ও refeeding risk কমা পর্যন্ত
  • কেন use হয়: Refeeding syndrome-এর central biochemical abnormality হলো hypophosphataemia; severe হলে respiratory failure, arrhythmia, rhabdomyolysis হতে পারে
  • Side effects: diarrhoea, hypocalcaemia, hyperphosphataemia; IV দিলে arrhythmia risk
  • Interaction: calcium/iron/magnesium antacid phosphate absorption কমাতে পারে; renal disease হলে toxicity risk
  • Clinical note: Refeeding syndrome সন্দেহে phosphate, magnesium, potassium close monitoring জরুরি।
  • Use: মূলত bowel cleansing/colonoscopy prep বা osmotic laxative; MedEx-এ sodium phosphate hypophosphataemia management-এও উল্লেখ আছে, কিন্তু এই preparation সাধারণত phosphate replacement হিসেবে নিজে নিজে ব্যবহার করা ঠিক নয়।

৫. Magnesium replacement

  • Generic: Magnesium oxide PO / Magnesium sulfate IV
  • Tablet 5.Magnox 365mg AS A  Magnesium oxide AS A Antacids, Electrolytes preparations, Oral electrolytes preparations.
  • Dose: Lab-based; mild deficiency PO, severe/symptomatic deficiency IV hospital setting
  • Duration: serum Mg²⁺ normal হওয়া পর্যন্ত
  • কেন use হয়: hypomagnesaemia arrhythmia, weakness, seizure এবং refractory hypokalaemia তৈরি করতে পারে
  • Side effects: diarrhoea, flushing; IV overdose → hypotension, bradycardia, respiratory depression
  • Interaction: tetracycline/quinolone/levothyroxine/bisphosphonate absorption কমায়; renal impairment-এ toxicity risk
  • Clinical note: K⁺ correction failure হলে Mg²⁺ check/correct করতে হবে।

৬. Olanzapine — off-label adjunct

  • Generic name: Olanzapine
  • Tablet 2.Deprex 5 mg AS A  Olanzapine AS A Atypical neuroleptic drugs.
  • Class: Second-generation atypical antipsychotic
  • Dose: Start 1.25–2.5 mg PO at night; titrate slowly to 2.5–10 mg/day depending tolerance/response
  • Duration: 8–12 weeks trial; benefit হলে 12–16 weeks বা specialist plan অনুযায়ী; long-term use হলে metabolic monitoring mandatory
  • কেন use হয়: AN cure নয়; severe weight-gain anxiety, rigid/obsessional thinking, agitation, insomnia, poor weight gain থাকলে adjunct হিসেবে consider করা হয়। Adult outpatient RCT-তে olanzapine placebo-এর তুলনায় modest BMI gain দেখিয়েছে, কিন্তু psychological obsessionality-তে clear benefit দেখায়নি।
  • Side effects: sedation, increased appetite/weight gain, constipation, dry mouth, orthostatic hypotension, metabolic syndrome, hyperglycaemia/diabetes risk, dyslipidaemia, raised prolactin less common than risperidone, EPS rare, QT prolongation rare, NMS rare
  • Monitoring: weight, waist, fasting glucose/HbA1c, lipid profile, BP, LFT, ECG if QT/electrolyte risk
  • Interaction: alcohol/CNS depressant → sedation বেশি; fluvoxamine/ciprofloxacin CYP1A2 inhibitor → olanzapine level বাড়ায়; carbamazepine/smoking CYP1A2 induction → level কমায়; QT-prolonging drug ও hypokalaemia থাকলে ECG caution। FDA label CNS-acting drugs/alcohol-এর সাথে caution এবং metabolism-related dose caution উল্লেখ করে।

৭. Fluoxetine — comorbid depression/OCD/anxiety থাকলে

  • Generic name: Fluoxetine
  • Capsule 1.Prolert 20 mg AS A Fluoxetine Hydrochloride AS A Phenothiazine related drugs..
  • Class: SSRI
  • Dose: Start 10–20 mg PO morning; usual 20–60 mg/day
  • Duration: comorbid depression/OCD/anxiety remission হলে সাধারণত 6–12 months continue; response assess 6–8 weeks
  • কেন use হয়: Low-weight acute AN বা weight gain-এর primary treatment হিসেবে নয়। Weight restoration-এর পরে persistent depression/OCD/anxiety থাকলে ব্যবহার করা যায়। 2006 JAMA RCT fluoxetine after weight restoration-এ overall relapse prevention benefit দেখাতে পারেনি।
  • Side effects: nausea, diarrhoea, insomnia, headache, anxiety activation, sweating, sexual dysfunction, hyponatraemia/SIADH, bleeding risk, QT risk, serotonin syndrome, young patients-এ suicidal thinking monitoring
  • Interaction: MAOI/linezolid/methylene blue contraindicated; tramadol, triptan, lithium, buspirone, St John’s wort, fentanyl → serotonin syndrome risk; NSAID/aspirin/warfarin/DOAC → bleeding risk; pimozide/thioridazine contraindicated/QT risk; CYP2D6 inhibition করে TCA, some antipsychotic, beta-blocker level বাড়াতে পারে। FDA fluoxetine label serotonergic drugs ও QT-related contraindicated drugs সম্পর্কে warning দিয়েছে।

৮. Sertraline / Escitalopram — alternative SSRI

  • Generic: Sertraline or Escitalopram
  • Tablet 1.Repose 50 Mg AS A Sertraline Hydrochloride AS A SSRIs & related anti-depressant drugs.
  • Dose:
    • Sertraline: 25–50 mg/day start; usual 50–200 mg/day
    • OR
    • Escitalopram: 5–10 mg/day start; usual 10–20 mg/day
    • Tablet 1.Esita 10 mg AS A Escitalopram Oxalate SSRIs & related anti-depressant drugs.
  • Duration: comorbid anxiety/depression/OCD থাকলে 6–12 months after remission
  • কেন use হয়: AN primary treatment নয়; comorbid depression/anxiety/OCD management
  • Side effects: GI upset, insomnia/somnolence, sexual dysfunction, hyponatraemia, bleeding risk, serotonin syndrome; escitalopram বেশি dose-এ QT risk
  • Interaction: MAOI/linezolid/methylene blue contraindicated; serotonergic drugs, NSAID/anticoagulants, QT-prolonging drugs caution
  • Clinical note: severe malnutrition/electrolyte imbalance থাকলে SSRI effect কম হতে পারে এবং side effect risk বেশি হতে পারে; NICE medication prescribing-এ malnutrition ও compensatory behaviour-এর impact বিবেচনা করতে বলেছে।

৯. Calcium + Vitamin D

  • Generic: Calcium carbonate/citrate + Cholecalciferol
  • Tablet 9.Reefcal-D (500mg+200IU) AS A (Coral Calcium+Vitamin D3) AS A Specific mineral & vitamin combined preparations.
  • Dose: Dietary intake অনুযায়ী; common adult target elemental calcium total 1000–1200 mg/day + vitamin D 800–1000 IU/day
  • Duration: deficiency/low bone density থাকলে months to long-term; DEXA/25-OH vitamin D অনুযায়ী
  • কেন use হয়: AN-এ low bone mineral density/osteoporosis risk কমাতে supportive therapy; কিন্তু প্রধান চিকিৎসা হলো healthy weight restoration
  • Side effects: constipation, hypercalcaemia, renal stone risk
  • Interaction: calcium levothyroxine, tetracycline, quinolone, iron, bisphosphonate absorption কমায়; 4 hours gap রাখা ভালো
  • Clinical note: NICE বলেছে low bone mineral density prevent/treat করার প্রধান উপায় হলো healthy body weight/BMI maintain করা।

৮) Prevention — কীভাবে প্রতিরোধ/relapse prevention করবেন

  1. Crash diet বন্ধ করা: rapid dieting, fasting, extreme calorie restriction avoid.
  2. Early screening: adolescent girls/boys, athletes, dancers, models, diabetes patients, chronic GI complaints বা unexplained weight loss থাকলে screen.
  3. Family education: খাবার নিয়ে blame/shame নয়; supportive meal environment তৈরি।
  4. Body image education: social media thin-ideal exposure কমানো, healthy body diversity শেখানো।
  5. Comorbid anxiety/depression/OCD early treatment.
  6. Regular follow-up: weight, vitals, electrolytes, menstrual function, mood, suicide risk।
  7. Relapse plan: trigger list, meal plan, family contact, therapist follow-up, warning signs — weight loss, meal skipping, excessive exercise, body checking।
  8. Avoid unsupervised laxative/diuretic/diet pill use. NICE laxative/diuretic misuse-এ gradual reduction এবং এগুলো calorie absorption কমায় না—এটা explain করতে বলেছে।

Overview / Summary

Anorexia Nervosa হলো severe psychiatric + medical eating disorder, যেখানে low body weight, weight gain fear, body image distortion থাকে। Diagnosis clinical, কিন্তু investigation জরুরি cardiac, electrolyte, endocrine, bone এবং refeeding risk detect করার জন্য। চিকিৎসার mainstay হলো nutritional rehabilitation, psychotherapy, family support, medical monitoring। Medication কখনো একা treatment নয়; thiamine/electrolytes refeeding complication prevention/correction-এর জন্য, আর olanzapine/SSRI selected adjunct বা comorbidity-targeted use।

Actionable Plan / Steps

  1. BMI, vitals, ECG, electrolytes, Mg, PO₄, glucose, renal/LFT urgent check করুন।
  2. Bradycardia <40/min, syncope, severe dehydration/electrolyte imbalance, QT prolongation, organ failure বা suicidal risk থাকলে urgent admission।
  3. Eating disorder specialist + dietitian + psychiatrist + physician team involve করুন।
  4. Refeeding শুরু করলে thiamine, multivitamin, K/Mg/PO₄ monitoring করুন।
  5. Adults: CBT-ED/MANTRA/SSCM; adolescents: FT-AN first-line।
  6. Medication only adjunct: olanzapine for severe weight-gain anxiety/rigidity; SSRI only comorbid depression/OCD/anxiety, usually after nutritional stabilization।

Reference List — Textbook + Guideline + DOI

Textbook

  1. Harrison’s Principles of Internal Medicine, 21st ed. Eating disorders/psychiatric disorders section.
  2. Davidson’s Principles and Practice of Medicine, 24th ed. Psychiatry and nutritional consequences section.
  3. Kaplan & Sadock’s Synopsis of Psychiatry, 12th ed. Feeding and Eating Disorders chapter.
  4. DSM-5-TR, American Psychiatric Association, Feeding and Eating Disorders: Anorexia Nervosa criteria.

Guidelines

  1. NICE Guideline NG69: Eating disorders: recognition and treatment; published 2017, updated 2020, reviewed 2024.
  2. American Psychiatric Association: Practice Guideline for the Treatment of Patients With Eating Disorders, 4th ed., 2023.
  3. Royal College of Psychiatrists: Medical Emergencies in Eating Disorders — MEED, CR233, 2022.
  4. NICE CG32: Nutrition support for adults — refeeding risk and nutrition support principles.

Peer-reviewed DOI

  1. Attia E, et al. Olanzapine versus placebo in adult outpatients with anorexia nervosa: randomized clinical trial. Am J Psychiatry. 2019;176:449–456. DOI: 10.1176/appi.ajp.2018.18101125.
  2. Walsh BT, et al. Fluoxetine after weight restoration in anorexia nervosa: randomized controlled trial. JAMA. 2006;295:2605–2612. DOI: 10.1001/jama.295.22.2605.
  3. Solmi M, et al. Comparative efficacy and acceptability of psychological interventions for adult outpatients with anorexia nervosa. Lancet Psychiatry. DOI: 10.1016/S2215-0366(20)30566-6.
  4. Treasure J, Duarte TA, Schmidt U. Eating disorders. Lancet. 2020. DOI: 10.1016/S0140-6736(20)30059-3.

Md.Rafiqul Islam Lipu,Date:-14-05-2026 Thursaday Time:-04-36-33 Pm

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